Angiotensin II modulates calponin gene expression in rat vascular smooth muscle cells in vivo

Objectives It has been shown that angiotensin II (Ang II) induces the expre ssion of calponin, a 34 kD actin-binding protein, in vascular smooth muscle cells in vitro. The aim of this study was to investigate whether Ang II ca n modulate calponin gene expression in rat aorta in vivo. Design Aortic calponin gene expression was studied after chronic exogenous Ang II administration and in Goldblatt hypertension. Methods To investigate the effect of Ang II administration, Sprague Dawley rats were treated for 6 days with a continuous infusion of Ang II (200 ng/k g per min) or saline by osmotic minipumps. The effect of endogenous Ang II on aortic calponin mRNA expression was studied in Goldblatt hypertensive ra ts with (2K1C model), or without (1K1C model) activation of the renin-angio tensin system. In particular, calponin gene expression in 2K1C rats was stu died both at 1 week (2K1C-HR, high renin) and 4 weeks after the onset of hy pertension, when plasma renin activity (PRA) was returned to normal values (2K1C-NR, normal renin). Systolic blood pressure (SBP) was measured twice a week. At the end of the experimental period, PRA was measured by radioimmu noassay, and aortic calponin gene expression was measured by Northern hybri dization. Results SBP was significantly higher (P < 0.01), whereas PRA was suppressed (P < 0.01), in Ang II versus saline-treated rats. Northern hybridization s howed that the aortic calponin gene expression significantly increased (2.5 -fold) in Ang II-treated rats (P = 0.01). In Goldblatt hypertensive rats, S BP was significantly higher in 2K1C-HR (P < 0.01), 2K1C-NR (P < 0.01) and 1 K1C (P < 0.01) rats compared with the corresponding sham-treated rats. Acti vation of the renin-angiotensin system was present only in 2K1C-HR rats (P < 0.01), and Northern analysis showed that aortic calponin mRNA expression was significantly increased (2.2-fold) in this group of rats only (P < 0.01 ). Conclusions Our data demonstrate that both exogenous and endogenous Ang II increase calponin gene expression in aortic smooth muscle cells, independen tly of the hemodynamic effect of Ang II. (C) 2001 Lippincott Williams & Wil kins.